Antioxidant activity and toxicity of ethylmethylhydroxypyridine succinate and edaravone: comparative in vitro experiment

02.02.2022
|In Pre-clinical & Experimental Studies
|By karateeva

Author:
A.V. SHCHUL’KIN, YU.V. ABALENIKHINA, P.D. EROKHINA, AND E.N. YAKUSHEVA

Ryazan State Medical University, ul. Vysokovoltnaya 9, Ryazan, 390026 Russia

Summary:
The cytotoxic effect and antioxidant activity of ethylmethylhydroxypyridine succinate (EMHPS) and edaravone were compared in a concentration range of 5 – 5000 mM. The cytotoxic effect was assessed on the HEK293 cell line using the MTT test. The oxidative stress (OS) was modeled by incubation of cells with hydrogen peroxide (Н2О2) at a concentration of 5 mM for an exposure duration of 24 h. The antioxidant activity of both substances was analyzed using their effects on the level of carbonyl derivatives of proteins and TBA-reactive products in the lysate of HEK293 cells. EMHPS reduced the viability of cells only at a concentration of 5 mM to 64.46 + 9.17% (p = 0,021), while edaravone was effective at concentrations of 5, 1, and 0.5 mM by reducing the viability of
cells to 44.55 + 7.43% (p = 0,008), 57.11 + 11.79% (p = 0,013), and 67.97 + 28.07% (p = 0,059), respectively. The OS modeling was accompanied by decrease in the viability of cells to 24.50 + 14.14% (p = 0,033). Both EMHPS and edaravone at concentrations of 50 and 100 mM prevented decrease in the cell viability under OS conditions. However, the EMHPS effect at a concentration of 100 mM was stronger by 30.6% ( p = 0.054) than that of edaravone at a similar concentration in reducing the content of carbonyl derivatives of proteins in the cell lysate. At concentrations of 100 and 50 mM, EMHPS decreased the level of TBA-reactive products in the lysate also stronger than did edaravone – by 43.8% ( p = 0.003) and 38.7% ( p = 0.05), respectively. Thus, results of this study show that EMHPS is a less toxic substance and has more pronounced antioxidant properties in comparison to edaravone.

Keywords: ethylmethylhydroxypyridine succinate; edaravone; oxidative stress; hydrogen peroxide; HEK293 cell line; toxicity; viability.